Case Of Ewing's Sarcoma Research Articles

Prognostic Modeling for Bone Sarcomas Based on a Large Prospective Cohort From a Tertiary Care Cancer Center in India

PURPOSE Outcomes of adolescents and young adults (AYA) with bone sarcomas including osteosarcoma (OGS) and Ewing sarcoma (ES) are affected by various factors including inadvertent previous treatment and poor compliance. We aimed to develop a risk-scoring system derived and validated at a tertiary care cancer center in India. METHODS All AYA OGS and ES cases treated at our institute with OGS-12 and Ewing’s family of tumors-2001 (EFT-2001) protocols from 2011 to 2021 and 2013 to 2018, respectively, were prospectively analyzed. Weighted scores provided to each prognostic variable on the basis of approximate ratios of the beta coefficients of each factor in the multivariable model were summated to divide patients into three clinically discriminatory risk groups, validated by applying separately to derivation, validation, and whole cohorts. RESULTS Among 606 (81.0%) of 748 AYA with nonmetastatic OGS, significant factors included in the prognostic model were failure to complete protocol (hazard ratio [HR], 2.65), previous treatment (HR, 2.93), necrosis <90% (HR, 1.63), joint involvement (HR, 2.0), and serum alkaline phosphatase >median (204 U/L; HR, 1.63). Of 104 (39.5%) of 263 AYA with ES, significant factors were failure to complete protocol (HR, 2.84), previous treatment (HR, 6.37), necrosis <100% (HR, 8.73), and tumor size >8 cm (HR, 2.64). For 142 (38.8%) of 366 AYA with metastatic OGS, significant factors were failure to complete protocol (HR, 5.29), metastases not amenable to local treatment (HR, 1.96), necrosis <90% (HR, 1.96), and >10 metastases (HR, 2.44). For 38 (43.6%) of 82 AYA with metastatic extremity ES, significant factors were failure to complete protocol (HR, 3.88) and metastases not amenable to local treatment (HR, 10.6). CONCLUSION We developed simple, effective prognostic models for AYA with bone sarcomas with specific potential relevance for low- and middle-income countries.

Vascularized fibular grafting following tumor resection demonstrates acceptable long-term outcomes in Denmark: a national retrospective cohort study.

Vascularized fibular grafting following tumor resection is an essential treatment option in limb salvage surgery. We aimed to evaluate: (I) bone healing, (II) complications and reoperations, (III) limb salvage, and (IV) survival. We present a retrospective evaluation of a national cohort comprising 27 patients. The indications were 13 cases of Ewing sarcoma, 12 cases of osteosarcoma, and 2 cases of giant cell tumor. The median age at surgery was 16 years (interquartile range [IQR] 10-18), and the median follow-up was 82 months (IQR 32-101). Patients were analyzed overall, as well as in subgroups based on tumor location (upper versus lower extremity) and pathology (osteosarcoma versus Ewing sarcoma). The primary rate of graft union was 63%, and after secondary procedures the overall rate of graft union was 67%, with a median time to union of 13 months (IQR 9-17). The reoperation rate was 74%, while the limb salvage rate was 93%. The 5-year overall survival rate was 81% (95% confidence interval [CI] 61-92). Patients with upper extremity tumors were more likely to attain graft union (risk ratio [RR] 5.5, CI 1.3-31.5) and less likely to undergo multiple reoperations (RR 0.3, CI 0.8-0.9) than patients with lower extremity tumors. Vascularized fibular grafting following tumor resection was associated with a graft union rate of 67%, a high frequency of reoperations, a high limb salvage rate (93%), and a 5-year survival rate of 81%.

Primary and Metastatic Pancreatic Ewing Sarcomas: A Case Report and Review of the Literature.

Ewing sarcomas are rare tumors arising mainly in the bones and the surrounding soft tissues. Primary extraosseous Ewing sarcomas have also been described in several other organs and locations other than bones, including the pancreas. These tumors have well-defined histological, immunohistochemical, and molecular characteristics. In this manuscript, we present a case of primary Ewing sarcoma of the pancreas in a 29-year-old patient, and we systematically review the literature on both primary and metastatic Ewing sarcomas of the pancreas, describing their clinicopathological characteristics. We also discuss the differential diagnosis and the treatment of this rare entity.

Ewing Sarcoma of the Sinonasal Tract: A Scoping Review.

Ewing sarcoma (ES) is a rare aggressive malignancy that can present in the sinonasal region. The objective of this study is to investigate the demographics, presentation, management, and outcomes of patients with sinonasal ES. PubMed, Web of Science, SCOPUS, CINAHL, and Cochrane Library. A scoping review of cases of sinonasal ES was performed. Inclusion criteria consisted of case reports, series, or retrospective reviews. 785 total articles were retrieved. 72 articles met inclusion criteria and were included in the final review for a total of 93 cases. 48 (53%) patients were male. Mean age at diagnosis was 26.4 years old (range 1-89). Nasal obstruction (N = 55, 59%), epistaxis (N = 35, 38%), and impaired vision (N = 29, 29%) were the most common symptoms. On examination, 38 (41%) patients had a nasal cavity mass. Most tumors (N = 33, 35%) were located in the maxillary sinus. 44 (47%) were left sided and 4 (4%) were bilateral. The most utilized treatment modalities were surgical resection with adjuvant chemoradiotherapy (N = 27, 29%), chemoradiotherapy alone (N = 24, 26%), and surgical resection with adjuvant chemotherapy (N = 14, 15%). 56 patients had no evidence of disease (60%), 14 patients died with disease (15%), and 9 patients were alive with disease (10%) at the time of follow-up. To our knowledge, we report the first scoping review of sinonasal ES. Patients generally present with non-specific sinonasal symptoms. Surgery with adjuvant chemoradiation is the most common treatment modality for these patients. NA Laryngoscope, 2024.

PATTERN OF CHEMOTHERAPY INDUCED TOXICITIES IN CHILDREN WITH EWING SARCOMA: A CASE SERIES

Background: Ewing sarcoma is a rare and aggressive bone or soft tissue cancer that primarily affects children and adolescents. Estimated incidence of Ewing sarcoma is reported to be 1.2-2.9 in one million individuals in England and 1 in one million in the US. Objective was to determine the pattern, and influence of gender and age on chemotherapy-induced toxicities in children with Ewing sarcoma. It was a descriptive case series conducted at the Department of Pediatric Oncology, CMH Rawalpindi, from January 2014 to June 2023. Methods: Children of either gender aged less than 18 years and diagnosed cases of Ewing Sarcoma were enrolled. All patients were given VIDE (vincristine, ifosamide, doxorubicin, etoposide) chemotherapy and patients were observed for chemotherapy induced toxicities. Chi square test was used to analyze significance of age and gender on toxicity. Results: In a total of 59 children 35 (59.3%) were male and 24 (40.7%) female. Out of these 11 children expired. The mean age was 7.59±3.87 years. Younger age was strongly associated with higher occurrence of toxicity specifically children under 5 years being most affected (p<0.05). Neutropenia, nausea and vomiting, thrombocytopenia, and diarrhea were the most frequent adverse events observed in 53 (89.9%), 37 (62.7%), 36 (61.0%), and 36 (61.0%) patients respectively. There was no association of gender with chemotherapy induced toxicity. Neutropenic sepsis and diarrhea were positively associated with mortality in the 11 children who expired (p<0.05). Conclusion: Neutropenia, nausea and vomiting, mucositis, thrombocytopenia and diarrhea were the most frequent chemotherapy induced toxicities in children with Ewing sarcoma. Younger children specifically under 5 years have a higher chance of chemotherapy induced toxicities however gender did not seem to influence related toxicities. Neutropenic sepsis was the major predictor of mortality warranting higher vigilance and aggressive management of infections.

Outcome of Ewing sarcoma in children: Twenty years experience from a single center

ABSTRACT Objective: Ewing sarcoma (ES) is a significant malignancy in pediatric patients, with a notable impact on bone health. Despite advances in treatment, ES still poses challenges, particularly in cases of metastasis or relapse. This study aims to evaluate the outcomes of ES in children treated at our center over a twenty-year period. Patients and Methods: We retrospectively reviewed pediatric patients diagnosed with ES at our center between January 2004 and February 2024. Data including demographic information, tumor characteristics, treatment modalities, and survival outcomes were analyzed. Results: Among 986 pediatric solid tumor cases, 137 (13.8%) were diagnosed with ES. After excluding ineligible cases, 115 ES cases were included in the study. The most common sites of involvement were the lower extremities. Metastatic disease was observed in 35.8% of cases, with the lungs being the most common site. Advanced age, and pelvic involvement were associated with poor prognosis. Histopathological response to neoadjuvant chemotherapy, represented by tumor necrosis rate, metastatic and relapse disease significantly influenced survival outcomes. Conclusion: Despite multimodal therapies, ES in children, especially with metastatic disease or relapse, presents a challenging prognosis. Early diagnosis and the development of novel treatment strategies are imperative to improve outcomes for these patients.

Ewing Sarcoma in the Pediatric Population: Predictors of Survival Within the United States.

Bone and joint tumors are the third most common cause of pediatric cancer-related deaths in the United States. Although there have been improvements in survival rates among pediatric cancer patients over the past few decades, bone and joint cancers remain the exception. Considering current clinical trials involving novel targeted therapies, the establishment of updated mortality rates and predictors of survival for this cancer would be prudent. This investigation sought to determine updated 5-year survival rates and predictors of survival among pediatric Ewing sarcoma (ES) of bone treated within the United States. The National Cancer Database was retrospectively inquired for all pediatric ES cases within the most updated bone and joint public use file available in September 2022. The reported data were truncated to only include patients with reported 5-year vital (ie, survival) status. Cox proportional hazard regression was conducted on both the truncated data and the entire cohort to validate the findings. The patients were then separated into alive versus deceased cohorts, and univariate regression analysis was done followed by multivariable regression of notable variables of interest. Overall, an aggregated 5-year survival rate of 74.5% was found in the included patient cohort. Patients with localized cancer had a comparatively improved 5-year survival rate of 84.70% as opposed to those with macrometastatic disease on presentation with a survival rate of 50.4%. Patient demographic-, tumor-, and treatment-specific variables all demonstrated an effect on survival. The multivariable predictors of worse mortality were found to include older age, larger tumor size (>8 cm), macrometastatic disease on presentation, and positive surgical margins. This analysis serves to establish updated survival rates of pediatric ES treated within the United States to set standards for comparison among future studies. Continued multi-institutional and international collaboration is needed to optimize current treatment results and develop novel targeted therapies.

Lung and bone metastases patterns in Ewing sarcoma: Chemotherapy improves overall survival.

Ewing sarcoma (ES) is a small round cell malignancy, mainly in the bone tissue, followed by the soft tissue. Lung metastases (LM) and bone metastases (BM) are the most common types of metastases. From 2010 to 2018, the Surveillance, Epidemiology, and End Results database diagnosed 242 cases of ES with LM, 186 cases of ES with BM, and 74 cases of ES with LM and BM. Univariate and multivariate logistic regression analyses were used to determine the risk factors for LM and/or BM, and Kaplan-Meier curves and Cox regression analysis were used to determine the prognostic factors for LM and/or BM. Tumor size ≥50 mm, N1 stage, BM, liver metastases, and surgical treatment were significantly correlated with LM; tumor size >100 mm, brain metastases, LM, surgical treatment, and chemotherapy were significantly correlated with BM; female, N1 stage, brain metastases, liver metastases, and surgical treatment were significantly correlated with LM and BM. Older age, BM, higher T stage, no surgical treatment, and no chemotherapy were harmful to the survival of ES patients with LM; older age, female, LM, and no chemotherapy were harmful to the survival of ES patients with BM; older age and no chemotherapy were harmful to the survival of ES patients with LM and BM. Larger tumor size, N1 stages, and organ metastases were significantly associated with ES patients with LM and/or BM. Chemotherapy is effective in improving the survival.

A rare case of extradural Ewing sarcoma of the cervical spine in a 9-year-old boy

Pediatric embryonal tumors have a rare occurrence in the peripheral nervous system. A more aberrant location is the extradural space, with only 25 cases being reported in literature. The seemingly innocuous symptoms can often be misleading as a sprain, and in our country, where tuberculosis is endemic, it can even be perceived as Pott’s spine, and therefore, leads to a delayed intervention for these rapidly progressive malignancies. We report the case of a 9-year-old boy whose symptoms started with a dull neck pain that was ignored for 6 months as a neck sprain. X-ray of his cervical spine showed only subtle loss of cervical lordosis, a finding that was missed. Eventually, he developed weakness of the right upper and lower limbs and was referred to our hospital. Magnetic resonance imaging revealed a large lobulated extradural lesion extending from C1-D3 level of neoplastic etiology. Postlaminectomy, the histopathology was consistent with primitive embryonal tumor. The patient was immediately started on an intensive chemotherapy regimen and is currently in the consolidation phase.

Consensus recommendations for systemic therapies in the management of relapsed Ewing sarcoma: A report from the National Ewing Sarcoma Tumor Board.

Ewing sarcoma (ES) is a malignant tumor of bone and soft tissue that most often occurs in children, adolescents, and young adults. Debate and controversy remain in the management of relapsed/refractory ES (RR-ES). The authors leveraged the expertise assembled by the National Ewing Sarcoma Tumor Board, a multidisciplinary virtual tumor board that meets monthly to discuss challenging cases of ES. In this review, they focus on select topics that apply to the management of patients with RR-ES. The specific topics covered include the initial approach of such patients and discussion of the goals of care, the role of molecular testing, chemotherapy regimens and novel agents to consider, the role of maintenance therapy, and the use of high-dose chemotherapy with autologous stem cell rescue. The data referenced are often limited to subgroup analyses and/or compiled from multiple sources. Although not intended to replace the clinical judgement of treating physicians, these guidelines are intended to support clinicians and provide some clarity and recommendations for the management of patients with RR-ES. PLAIN LANGUAGE SUMMARY: Ewing sarcoma (ES) is a bone and soft tissue cancer that most often occurs in teenagers and young adults. This article uses the experience of the National Ewing Sarcoma Tumor Board, a multi-institution, multidisciplinary virtual tumor board that meets monthly to discuss challenging cases of ES and to address questions related to the treatment of patients with relapsed ES. Although not intended to replace the clinical judgement of treating physicians and limited by available data, these consensus recommendations will support clinicians who treat patients with this challenging malignancy, made even more difficult when it recurs.

Extraskeletal Ewing Sarcoma of the Extremities and Trunk: A Retrospective Analysis of a Mono-Institutional Series

Introduction: Extraskeletal Ewing sarcoma (EEwS) is a rare malignant tumor, and current international recommendations indicate systemic and local treatment like bone Ewing sarcoma (BEwS); to the best of our knowledge, very few studies tried to explore the clinical and genetic characteristics of this tumor, and the most appropriate treatment strategy remains uncertain. Methods: We reviewed 35 EEwS cases enrolled at Rizzoli Orthopedic Institute in Bologna, Italy, between 1988–2022. We performed RNA sequencing in 18 Ewing sarcoma cases, including 12 BEwSs and 6 EEwSs. We analyzed overall survival (OS), local relapse-free survival (LRFS), and metastasis-free survival (MFS) and the risk factors associated to survival. Results: Unsupervised hierarchical clustering showed no differences in the transcriptional profile between EEwS and BEwS. Five-year OS was 67% (95% confidence interval [CI]: 47–80), 5-year LRFS was 61% (95% CI: 43–75), and 5-year MFS was 55% (95% CI: 38–70). Recurrent tumors, larger than 8 cm, and elevated lactate dehydrogenase (LDH) serum value resulted to be negative prognostic factors. Conclusions: The finding/detection of a genetic profile that is indistinguishable between EEwS and BEwS confirms the view that the two subgroups belong to the same tumor entity and supports the use of a single therapeutic approach for Ewing sarcoma, regardless of the site of origin. Statistical evaluation showed that size bigger than 8 cm, elevated LDH, and recurrent tumors had a worse prognosis, suggesting a risk-stratification method for identifying patients for specific therapy treatment. However, larger, multicenter, prospective trials are called for to validate our findings.

A case of extraosseous Ewing sarcoma diagnosed by EUS-FNA for a pancreatic tail mass

A case of extraosseous Ewing sarcoma diagnosed by EUS-FNA for a pancreatic tail mass

Extraskeletal Ewing Sarcoma of the Gastrointestinal and Hepatobiliary Tract: Deceptive Immunophenotype Commonly Leads to Misdiagnosis.

Ewing sarcoma (ES) is an uncommon mesenchymal neoplasm that typically develops as a bone mass, although up to 30% arise in extraskeletal sites. ES of the gastrointestinal (GI) and hepatobiliary tract is rare and may be misdiagnosed as other, more common neoplasms that occur in these sites. However, the correct classification of extraskeletal ES is important for timely clinical management and prognostication. We reviewed our experience of ES in the GI and hepatobiliary tract in order to further highlight the clinicopathologic features of these neoplasms and document the potential for misdiagnosis in this setting. The archives and consultation files of 6 academic institutions were retrospectively queried for cases of ES occurring in the GI and hepatobiliary tract. The histologic slides and ancillary studies were reviewed and clinical data were retrieved for each case through the electronic medical records, when available. Twenty-three patients with ES in the GI and/or hepatobiliary tract were identified from 2000 to 2022. Of these, 11 were women and 12 were men with a median age of 38 years (range, 2 to 64). Tumor locations included the pancreas (n=5), liver (n=2), stomach (n=3), colorectum (n=3), and small intestine (n=5), as well as tumors involving multiple organs, pelvis and retroperitoneum (n=5). Tumor size varied between 2cm and 18cm. Twenty were primary and 3 were metastases. Of the 23 cases, only 17% were initially diagnosed as ES. The most common misdiagnoses involved various forms of neuroendocrine neoplasia due to expression of synaptophysin and other neuroendocrine markers (22%). A wide variety of diagnoses including GI stromal tumor was considered due to aberrant CD117 expression (4%). The diagnosis of ES was ultimately confirmed by detection of the EWSR1 rearrangement in 22 cases. The remaining case was diagnosed using traditional immunohistochemistry. Follow-up information was available in 20 cases, with follow-up time varying between 2 and 256 months. Six patients with follow-up died of disease between 6 and 60 months following initial presentation. Our data indicate ES in the GI and hepatobiliary tract is commonly misdiagnosed leading to a delay in therapy. In light of the attendant therapeutic and prognostic implications, ES should be considered in the differential diagnosis of any GI or hepatobiliary tumor with epithelioid and/or small round cell morphology.

Synchronous Ewing sarcoma of the fibula with involvement of the orbit and abducens nerve palsy

Simultaneous or synchronous Ewing sarcoma (ES) is the occurrence of multifocal lesions without pulmonary involvement. This is a very rare condition. We present a case of multifocal synchronous ES of the fibula with orbital involvement and adducens nerve palsy. A 17-year-old boy presented with pain and swelling in both legs for 6 weeks. He was unable to walk due to pain. He was pale and cachexic. There was proptosis and ptosis in the right eye. His investigations were consistent with a multifocal malignant tumor. There were lesions in the left fibula, tibia, right tibia, and right orbit. The histopathological diagnosis was Ewing sarcoma (ES). This is the first report of synchronous ES involving the orbit and abducens nerve.

Detection of EWSR1 gene rearrangement by fluorescence in situ hybridization in bone and soft tissue tumors: clinical application evaluation and atypical signal analysis

Objective: To investigate the clinical application of EWSR1 gene rearrangement by fluorescence in situ hybridization (FISH) in bone and soft tissue tumors and to analyze the cases with atypical signal pattern. Methods: The cases detected for EWSR1 gene rearrangement by FISH in Beijing Jishuitan Hospital, Capital Medical University from 2014 to 2021 were collected, and the value of detecting EWSR1 gene rearrangement for diagnosing bone and soft tissue tumors was analyzed. The cases with atypical positive signals were further analyzed by next generation sequencing (NGS). Results: FISH using EWSR1 break-apart probe kit was successfully performed in 97% (205/211) of cases, 6 cases failed. Four of the 6 failures were due to improper decalcification, 1 case due to signal overlap caused by thick slices, and 1 case due to signal amplification and disorder. EWSR1 gene rearrangements were positive in 122 cases (122/205, 59%), atypical positive signal in 8 cases (8/205, 4%), and negative in 75 cases (75/205, 37%). In cases testing positive, the percentage of positive cells ranged from 34% to 98%, with 120 cases (120/122, 98%) showing a positive cell percentage greater than 50%. Among the 205 successfully tested cases, 156 cases were histologically diagnosed as Ewing's sarcoma, of which 110 were positive (110/156, 71%), 7 were atypical positive (7/156, 4%), and 39 were negative (39/156, 25%). Nine cases were histologically diagnosed as clear cell sarcoma of soft tissue, of which 6 were positive (6/9), 1 was atypical positive (1/9), and 2 were negative (2/9). Five cases were histologically diagnosed as extraskeletal myxoid chondrosarcoma, of which 2 were positive (2/5) and 3 were negative (3/5). Three cases were histologically diagnosed as angiomatoid fibrous histiocytoma, of which 2 were positive (2/3) and 1 was negative (1/3). Two cases were histologically diagnosed as myoepithelioma of soft tissue, of which 1 was positive (1/2) and 1 was negative (1/2). One case was histologically diagnosed as olfactory neuroblastoma with a positive result. The 29 other tumor cases including osteosarcoma, synovial sarcoma, and malignant melanoma and others were all negative. Basing on histology as the standard for diagnosis and considering atypical positive cases as negative, comparing with the 29 cases of other tumors as control group, the sensitivity for diagnosing Ewing's sarcoma through the detection of EWSR1 gene rearrangement was 71%, and the specificity was 100%; the sensitivity for diagnosing clear cell sarcoma of soft tissue was 67%, and the specificity was 100%; the sensitivity for diagnosing extraskeletal myxoid chondrosarcoma was 40%, and the specificity was 100%; the sensitivity for diagnosing angiomatoid fibrous histiocytoma was 67%, and the specificity was 100%; the sensitivity for diagnosing myoepithelioma of soft tissue was 50%, and the specificity was 100%; the sensitivity for diagnosing olfactory neuroblastoma was 100%, and the specificity was 100%. Four of 8 cases with atypical positive signals analyzed by NGS showed EWSR1 rearrangement, including EWSR1::FLI1 in one case of Ewing sarcoma, EWSR1::NFATC2 in one case of EWSR1::NFATC2-rearranged sarcoma, EWSR1::ATF1 in one case of clear cell sarcoma of soft tissue and EWSR1::NR4A3 in one case of extraskeletal myxoid chondrosarcoma. Conclusions: Detection of EWSR1 rearrangement by FISH is of utmost significance in the diagnosis of bone and soft tissue tumors. Cases with atypical positive signals should be further scrutinized, correlating with their histomorphology and verifying by NGS if necessary.

Clinicopathological and molecular genetic analysis of 13 cases of primary retroperitoneal Ewing sarcoma

Retroperitoneal Ewing sarcomas (RES) are very rare and mostly described in case reports. The purpose of this study was to retrospectively analyze the clinicopathology, molecular characteristics, biological behavior, and therapeutic information of 13 cases of primary RES with immunohistochemical staining, fluorescence in situ hybridization, RT-PCR and NGS sequencing detection techniques. The thirteen patients included eight males and five females with a mean age of 34 years. Morphologically, the tumors were comprised of small round or epithelial-like cells with vacuolated cytoplasm (6/13,46 %) arranged in diffuse, nested (8/13,62 %) and perivascular (7/13,54 %) patterns. Unusual morphologic patterns, such as meningioma-like swirling structures and sieve-like structures were relatively novel findings. Immunohistochemical studies showed CD99 (12/13; 92 %), CD56 (11/13; 85 %), NKX2.2 (9/13; 69 %), PAX7 (10/11;91 %) and CD117(6/9;67 %) to be positive.12 cases (92 %) demonstrated EWSR1 rearrangement and 3 cases displayed EWSR1::FLI1 fusion by FISH. ERCC4 splice-site variant, a novel pathogenic variant, was discovered for the first time via RNA sequencing. With a median follow-up duration of 14 months (6 to 79 months), 8/13 (62 %) patients died, while 5/13(38 %) survived. Three cases recurred, and five patients developed metastasis to the liver (2 cases), lung (2 cases) and bone (1 case). RES is an aggressive, high-grade tumor, prone to multiple recurrences and metastases, with distinctive morphologic, immunohistochemical, and molecular genetic features. ERCC4 splicing mutation, which is a novel pathogenic variant discovered for the first time, with possible significance for understanding the disease, as well as the development of targeted drugs.

Primary intracranial peripheral primitive neuroectodermal tumor: lessons from an exceptionally rare neoplasm. Illustrative case.

The primary intracranial peripheral primitive neuroectodermal tumor (pPNET) is a lesion subtype within the Ewing sarcoma family of tumors. pPNETs are extremely uncommon pathologies, accounting for 0.03% of intracranial tumors and 1% to 2% of Ewing sarcoma cases. Given its histological aspect similar to other highly proliferative malignant neuroectodermal neoplasms, pPNET merits extensive workup for accurate diagnosis and treatment. A 36-year-old male presented to the emergency department with a 1-year history of headaches in the right frontoparietal area, generalized tonic-clonic seizures, and a history of the resection of a tumor labeled as a meningioma 5 years before admission. He was neurologically intact. Brain magnetic resonance imaging revealed a heterogeneous focal lesion of 25 × 35 × 23 mm with a necrotic center and neoformative appearance in the right frontal cortex. The patient underwent multimodal treatment with gross-total resection, radiotherapy, and chemotherapy. Histopathological examination results supported the diagnosis of pPNET. At the 2-year follow-up, the patient had no new-onset symptoms, and brain imaging revealed absent signs of tumor recurrence. The present case describes an extraordinary pPNET case, initially confounded as a clear cell meningioma. Managing pPNET requires thorough investigation, careful differentiation from similar neuroectodermal lesions, and multimodal treatment to improve the patient's prognosis.

Primary extraskeletal intradural Ewing sarcoma with acute hemorrhage: a case report and review of the literature

BackgroundSpinal cord tumors present a challenge in diagnosis and treatment due to their varied histopathological characteristics. While Ewing sarcoma is a rare malignant tumor typically originating from skeletal bone, cases of primary intradural extraskeletal Ewing sarcoma are exceptionally rare. The similarity of its presentation to other spinal tumors further complicates its identification and management.Case presentationWe report a case of a 58-year-old Palestinian male with intradural extraskeletal lumbar Ewing sarcoma. The patient initially presented with lower back pain and bilateral S1 radiculopathy, with more severe symptoms on the left side. Magnetic resonance imaging revealed a 7 cm oval-shaped mass with homogeneous contrast enhancement, obstructing the spinal canal from L3/L4 to L5/S1 levels. Initially, a myxopapillary ependymoma was suspected, but the patient’s sensory and motor functions suddenly deteriorated during hospitalization. Repeat magnetic resonance imaging indicated heterogeneous contrast enhancement, indicating acute intratumoral hemorrhage. Consequently, the patient underwent emergent L3–L5 laminotomy, with successful gross total resection of the tumor. Histopathological and immunohistochemical analyses confirmed the diagnosis of intradural extraskeletal Ewing sarcoma. Adjuvant therapy was administered to minimize the risk of local recurrence or distant metastasis. A systematic review of relevant literature, along with retrospective analysis of medical records, operative reports, radiological studies, and histopathological findings of similar cases, was also conducted.ConclusionsIntradural extraskeletal Ewing sarcoma is an infrequently encountered condition in adult patients, emphasizing the importance of considering it in the differential diagnosis of spinal tumors. Surgeons must possess a comprehensive understanding of this rare entity to ensure accurate staging and optimal management, particularly in the early stages when prompt intervention may improve prognosis.

Divergent HLA variations and heterogeneous expression but recurrent HLA loss-of- heterozygosity and common HLA-B and TAP transcriptional silencing across advanced pediatric solid cancers.

The human leukocyte antigen (HLA) system is a major factor controlling cancer immunosurveillance and response to immunotherapy, yet its status in pediatric cancers remains fragmentary. We determined high-confidence HLA genotypes in 576 children, adolescents and young adults with recurrent/refractory solid tumors from the MOSCATO-01 and MAPPYACTS trials, using normal and tumor whole exome and RNA sequencing data and benchmarked algorithms. There was no evidence for narrowed HLA allelic diversity but discordant homozygosity and allele frequencies across tumor types and subtypes, such as in embryonal and alveolar rhabdomyosarcoma, neuroblastoma MYCN and 11q subtypes, and high-grade glioma, and several alleles may represent protective or susceptibility factors to specific pediatric solid cancers. There was a paucity of somatic mutations in HLA and antigen processing and presentation (APP) genes in most tumors, except in cases with mismatch repair deficiency or genetic instability. The prevalence of loss-of-heterozygosity (LOH) ranged from 5.9 to 7.7% in HLA class I and 8.0 to 16.7% in HLA class II genes, but was widely increased in osteosarcoma and glioblastoma (~15-25%), and for DRB1-DQA1-DQB1 in Ewing sarcoma (~23-28%) and low-grade glioma (~33-50%). HLA class I and HLA-DR antigen expression was assessed in 194 tumors and 44 patient-derived xenografts (PDXs) by immunochemistry, and class I and APP transcript levels quantified in PDXs by RT-qPCR. We confirmed that HLA class I antigen expression is heterogeneous in advanced pediatric solid tumors, with class I loss commonly associated with the transcriptional downregulation of HLA-B and transporter associated with antigen processing (TAP) genes, whereas class II antigen expression is scarce on tumor cells and occurs on immune infiltrating cells. Patients with tumors expressing sufficient HLA class I and TAP levels such as some glioma, osteosarcoma, Ewing sarcoma and non-rhabdomyosarcoma soft-tissue sarcoma cases may more likely benefit from T cell-based approaches, whereas strategies to upregulate HLA expression, to expand the immunopeptidome, and to target TAP-independent epitopes or possibly LOH might provide novel therapeutic opportunities in others. The consequences of HLA class II expression by immune cells remain to be established. Immunogenetic profiling should be implemented in routine to inform immunotherapy trials for precision medicine of pediatric cancers.

Rare origin - Ewing's sarcoma of the pleura: a case report and literature review

Ewing sarcoma (ES) was first reported by Ewing in 1921. It is the second largest malignant bone tumor in children and adolescents, typically occurring in the bones of trunk or limbs . Extraskeletal Ewing sarcoma (EES) was first reported by Tefft et al. in 1969 and is extremely rare, accounting for less than 1% of all sarcomas. It can occur in any part of soft tissue, mostly in the trunk and lower limbs, and rarely in the pleura. We report a 22-year-old case of extraosseous Ewing sarcoma of pleural origin discovered and pathologically confirmed by physical examination. We report its CT manifestations and pathological results, and review the literature to summarize and analyze the clinical and imaging characteristics of extraosseous Ewing sarcoma, in order to improve our understanding of the disease.